Adenovirus-Mediated Gene Transfer for Cystic Fibrosis: Safety of Single Administration in the Lung 
DESCRIPTION OF THE PROPOSED EXPERIMENT IN NON TECHNICAL LANGUAGE 
Cystic fibrosis (CF) is a common inherited disease among the white population of Europe and North America. It is 
characterized by chronic infection and obstruction of the airways leading to the lungs. Patients commonly die from the 
disease by their mid-to-late twenties. The recent discovery and characterization of the inherited material — the gene — 
that causes the disease has led to a rapid increase in our knowledge of the basic defect responsible for the disease 
state, and has raised the possibility of treating CF by giving to the patient a good copy of the CF-associated gene. This 
is a new approach to the treatment of inherited diseases, called gene transfer. 
Eventually gene transfer for cystic fibrosis might be achieved by treating the airways of CF patients with a 'tailor-made” 
virus that has been altered to make it less infectious and to include the CF gene. One possible virus to do this is called 
adenovirus. It is normally associated with minor respiratory infections, such as colds. Although adenoviruses have 
been used safely in the past as vaccines, we need to establish the feasibility and safety of using such an approach for 
treatment of cystic fibrosis. 
The authors of this proposal have already treated four CF patients with very small amounts of CF-adenovirus and 
shown it is possible to correct the basic defect associated with the disease. Virus was applied to a small area within the 
nose and a small electrode used to measure the tiny voltage that normally exists across the lining of the nose. In 
patients with CF, this voltage is abnormal because of a defect in the CF gene. After administration of virus, this voltage 
was restored to normal for the few days tested. 
We now hope to extend these studies to ascertain whether it is safe to administer vims to the lung in amounts that are 
believed to be large enough to correct the defect in the CF gene, a n d whe t he kv i r us x a n be introdu ced sa f e l y i nto t hc - 
Img-by- aeroso l tr e atme at — breafeiogJo^' jaist nf vims . To do this, virus will be applied to a small part of the lung (a 
lobe) first, in some patients, by a bronchoscope, a tube commonly used in pulmonary medicine which allows 
visualization of the airways. I f f K) -prdP fcfflc occur tho viruc wil t-b o - givon to - othor - pat ie nt6 - b y- aor o sol4reat ffi Qo t. Sy 
t oe i ng nnrrv»Al nHminir-tratinn nf tho yj n r l"nj| ?t? rfin 3 u, ith w i idn l y i i^ri ^ nrl 
nnnim/flen/o ppethr> d ^r linnjTWJlmu irt ^in hn nfnly ww^Uiittwiiir winirjioator. In t his way, Wfi h ope to mflX t mig e 
patient c afety] while at -the mmo t i me detnrmining-whnthgr ad ^ n A vinis is likely tff-h A - e a f Q -f ft r- UCQ in pati owfrr- 
Recombinant DNA Research, Volume 20 
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